title: Cathepsin L is involved in 6-hydroxydopamine induced apoptosis of SH-SY5Y neuroblastoma cells.
abstract: Our previous study reported that cathepsin L may contribute to the death of dopaminergic neurons in rodent model of Parkinson's disease (PD). In this study we detected the changes in the expression of lysosomal cathepsin L in cellular models of PD. In human neuroblastoma SH-SY5Y cells, treatment with 6-hydroxydopamine caused an increase in cathepsin L immunoreactivity in the cytoplasm and an increased production of the active form of cathepsin L. The contribution of cathepsin L to 6-OHDA-induced NF-κB activation and death of SH-SY5Y neuroblastoma cells were evaluated with an irreversible inhibitor of cathepsin L, Z-FY(t-Bu)-DMK. 6-OHDA-induced IκB-α degradation, NF-κB p65 nuclear translocation, p53 and PUMA expression were partially blocked by Z-FY(t-Bu)-DMK. In addition, Z-FY(t-Bu)- DMK modulated the Bcl-2 family levels, and suppressed caspase-3 activation. These data indicate that cathepsin L may be involved in 6-OHDA-induced apoptosis and Parkinsonian neurodegeneration.
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, 199 Ren Ai Road, Suzhou 215123, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Xiang
authors.forename: Xifeng
authors.initials: X
authors.lastname: Fei
authors.forename: Wenzhuo
authors.initials: W
authors.lastname: Zhuang
authors.forename: Yun
authors.initials: Y
authors.lastname: Fang
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Qin
authors.forename: Zhongqin
authors.initials: Z
authors.lastname: Liang
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D056668:Cathepsin L / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018663:Adrenergic Agents; D016328:NF-kappa B; D016627:Oxidopamine; D056668:Cathepsin L